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Acute selective bioactivity of grape seed proanthocyanidins on enteroendocrine secretions in the gastrointestinal tract.

ABSTRACT: Background: Enteroendocrine cells respond to food components by secreting an array of hormones that regulate several functions. We have previously shown that grape seed proanthocyanidins (GSPE) modulate GLP-1 levels. Objective: To deepen on the knowledge of the mechanisms used by GSPE to increase GLP-1, and extend it to its role at modulation of other enterohormones. Design: We used an ex vivo system to test direct modulation of enterohormones; STC-1 cells to test pure phenolic compounds; and rats to test the effects at different gastrointestinal segments. Results: GSPE compounds act at several locations along the gastrointestinal tract modulating enterohormone secretion depending on the feeding condition. GSPE directly promotes GLP-1 secretion in the ileum, while unabsorbed/metabolized forms do so in the colon. Such stimulation requires the presence of glucose. GSPE enhanced GIP and reduced CCK secretion; gallic acid could be partly responsible for this effect. Conclusions: The activity of GSPE modulating enterohormone secretion may help to explain its effects on metabolism. GSPE acts through several mechanisms; its compounds and their metabolites are GLP-1 secretagogues in ileum and colon, respectively. In vivo GLP-1 secretion might also be mediated by indirect pathways involving modulation of other enterohormones that in turn regulate GLP-1 release.

SUBMITTER: Casanova-Marti A

PROVIDER: S-EPMC5475339 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Acute selective bioactivity of grape seed proanthocyanidins on enteroendocrine secretions in the gastrointestinal tract.

Casanova-Martí Àngela À Serrano Joan J Blay M Teresa MT Terra Ximena X Ardévol Anna A Pinent Montserrat M

Food & nutrition research 20170607 1

Background: Enteroendocrine cells respond to food components by secreting an array of hormones that regulate several functions. We have previously shown that grape seed proanthocyanidins (GSPE) modulate GLP-1 levels. Objective: To deepen on the knowledge of the mechanisms used by GSPE to increase GLP-1, and extend it to its role at modulation of other enterohormones. Design: We used an ex vivo system to test direct modulation of enterohormones; STC-1 cells to test pur ...[more]

PMID: 28659730

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Project description:BACKGROUND:Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS:Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS:Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS:SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Dataset Information

Acute selective bioactivity of grape seed proanthocyanidins on enteroendocrine secretions in the gastrointestinal tract.

Publications

Acute selective bioactivity of grape seed proanthocyanidins on enteroendocrine secretions in the gastrointestinal tract.

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